Repeated Assessment of Methylprednisolone Pharmacokinetics During Chronic Immunosuppression in Renal Transplant Recipients

Abstract

Objective:

To compare the pharmacokinetics of methylprednisolone in renal transplant recipients on 2 occasions separated by at least 1 month during chronic immunosuppression.

Design:

A prospective unblinded trial.

Patients:

Ten renal transplant recipients (aged 25–62 years) evaluated in a public university-affiliated hospital clinic.

Interventions:

All patients received their chronic oral dose of methylprednisolone as a 10–20-minute intravenous infusion during the 2 study periods.

Main Outcome Measures:

Serum methylprednisolone concentrations were determined by HPLC and were used to generate the pharmacokinetic parameters of the drug.

Results:

During study 1, which ranged from 1.2 to 24 months posttransplant, the mean ± SD methylprednisolone dose was 13.2 ± 6.4 mg. In study 2 (2.5–38,5 mo posttransplant), the mean dose was 10.6 ± 3 mg. During both study periods, methylprednisolone concentrations exhibited a monoexponential decline. Considerable variability in methylprednisolone clearance was observed between periods in certain patients. Four of the 10 patients demonstrated a reduction in clearance from study 1 to study 2, which ranged from a 28% to a 53% decrease. Two patients exhibited an increase in clearance of 40% and 49%. The mean ± SD total body clearance in study I was 363 ± 330 mL/min/kg, whereas the mean volume of distribution was 1.18 ± 0.53 L/kg. The mean elimination rate constant was 0.29 ± 0.14 h⁻¹, with a mean serum half-life of 2.87 ± 1.15 h during the first phase. In study 2, the mean methylprednisolone clearance was 261 ± 150 mL/min/kg (p > 0.05) and the mean volume of distribution was 0.89 ± 0.31 L/kg (p > 0.05). The mean serum half-life of methylprednisolone was 2.91 ± 0.60 h (p > 0.05), with the mean elimination rate constant of 0.25 ± 0.06 h⁻¹(p > 0.05).

Conclusions:

These data demonstrate that intrapatient variability in methylprednisolone clearance exists among certain renal allograft recipients. As a result of the observed variability, patients who are continued on the same dose of methylprednisolone during the posttransplant period of chronic immunosuppression will be subjected to a changing pattern of exogenous glucocorticoid exposure. The impact of these changing patterns requires further prospective evaluation.